IMRT planning for HN cancr: Some clinical issues

Avraham Eisbruch

University of Michigan

Defining the targets

The GTV:

1. Clinical information: palpation, mirror/fiberoptic exam, direct endoscopy report

2. Imaging: Planning CT (contrast-enhanced)• Register with MRI / PET

Nasopharynx caCT

Nasopharynx caMRI

Using FDG-PET to define the GTV

• How exactly should PET be used?

• If the PET-based and CT-based GTVs differ, what is the “truth”?

Using PET-CT for GTV delineation

CT-GTVs

The GTVs on CT and FDG-PET usually correlate well

FDG-PET may define the GTV better than CT

Lt BOT cancer. The GTV is blurred by CT artifact

FDG-PET may define the GTV better than CT

Lt tonsil cancer. CT: Retropharyngeal node was part of the CTV. PET: it should be a GTV.

FDG-PET may be false negative: failure to detect obvious gross disease

#1

#2

#1

LN #2: extensive necrosis; not detected by PET

Primary ca Primary ca

PET may be false positive: Benign lymphatic tissue in the BOT accumulates FDG

Consult Nuc Med to verify that the signal intensity/SUV are right

Suspicious nodes on CT, PET (-): CTVs or GTVs?

?

? + +

Use clinical judgement

PET vs. other imaging modalities vs. LN pathology

Adams et al, Eur J Nuc Med 1998

Larynx cancer: Matching the surgical specimen, CT, and PET

Daisne, …Gregoire, Radiology 2004

Matching the surgical specimen, CT, MRI, and PET

• The GTVs according to PET were usually slightly smaller than the CT/MRI volumes

• No modality showed the extent of the primary with complete accuracy– evaluation of submucosal tumor extension was

deficient by all modalities.

Daisne, …Gregoire, Radiology 2004

Summary: Outlining the primary tumor GTV

• Use the PET and CT/MRI information for composite GTV delineation

• Add clinical examination results, especially for the mucosal extent of the gross disease

Summary: Outlining the nodal GTVs

• Wherever a node is PET (+), include in the GTV

• If CT is highly suspicious and PET is (-), include in the GTV.

• In borderline cases of (+) CT and (-) PET, use clinical judgement to define as GTV or CTV.

Can FDG-PET be used to define the CTVs?

• Sentinel node biopsy and neck dissection in the clinically (-) neck: nodes were examined by the pathologists at 2 mm slices

• Occult metastases (size 1.2-1.5 mm): in 5/12 patients;

• FDG PET correctly identified only one (sensitivity of 25%).

• We cannot rely on PET for outlying the CTV.

Stoeckli et al, Head Neck 2002

Outlining Lymph Node CTVs

• Which LN groups at at risk for each tumor site and stage?

• How should the LN be delineated on the planning CT?

Som et al.,Arch. Otolaryngol.Head Neck Surg.1999

Neck Node Levels

www.rtog.org/hnatlas/main.htm

Gregoire,Levendag, et al.

WWW.RTOG.ORG

Researchers

HN Atlas

Cranial-most extent of neck CTV

• In the clinically (-) non-nasopharyngeal ca:– The bottom of the transverse process of C1

• Gregoire et al

This will ensure coverage of the JD (sub-digastric) nodes

Rouviere, 1938

Oral cavity lymphatics

Rouviere, 1938

Pharyngeal lymphatics

What about nasopharyngeal cancer?

Lateral retroph. n

Junctional n.

Level II

Level V

Nasopharynx ca

Should we biopsy all non-specific parotid nodules?

IJROBP 2007

Parotidean LN metastases in NPC

Eustachian Tube: Lymphatic Drainage

In addition to sub-digastric and RPN: Lymphatics to parotidean nodes

H. Rouviere, 1932

Parotidean LN metastases in NPC

Due to retrograde flow when level II is heavily involved?

Tonsil ca, T3N2c

Parotidean LN metas

Primary Tu

No nasopharyngeal involvement…

…but significant ipsilateral level II nodal involvement

Parotidean metastases

• Risk of retrograde lymphatic drainage when level II is heavily involved

• Suggest: omit ipsilateral parotid sparing if ipsilateral level II is heavily involved.

Can we improve outcome by GTV dose escalation?

• Escalate doses to the whole GTV

• Escalate the doses to the parts of the GTV judged to be at highest risk

Escalate/accelerate doses to the whole GTV

• Baylor: “SMART”: 60 Gy/2.4 Gy/fraction

– BED2Gy 70 Gy, over 5 weeks

– Concurrent with chemotherapy: not tolerable due to acute mucositis• Amosson, ASTRO 2003

Escalate/accelerate doses to the whole GTV

• Nasopharynx ca: 64.8/2.4/fr. Over 5.5 weeks conc. with cisplatin– “modest increase in toxicities”

• WS Koom, Head Neck 2008

• Larynx/hypopharynx ca: 67.2 Gy/2.4 conc. with cisplatin– “acceptable acute toxicity”.

• Guerrero-Urbano , Radiother Oncol 2007

High fraction doses: Oropharyngeal ca

• RTOG 00-22: 66 Gy/30 fractions, no chemo– Few long-term complications

• 6% ORN• Eisbruch et al, IJROBP 2009

• Stanford: 66 Gy/30 fractions, conc. chemo– Few long-term complications

• Orocutaneous fistula, tracheal stenosis, ORN

• Daly ME et al, IJROBP 2009

Moderately high fraction doses: laryngeal/hypopharyngeal ca

• MSKCC: 70 Gy/32-33 fractions (2.12 Gy/fraction) conc with chemo– Late complications:

• 20% PEG dependency at 2 years• Laryngeal necrosis, necrotizing skin fascitis

• Lee NY, IJROBP 2007

Escalate the dose to part of the GTV

• The FDG-PET avid part of the GTV tumor

• Hypoxic regions within the GTV

CTV

• Outlining the CTV– Anatomically: taking into account the

compartments at risk– Uniformly, arbitrary margins: 1-2.5 cm

CTV Doses and their BED(2 Gy)(assuming alpha/beta 10 Gy and loss of 0.7 Gy/day of

extending treatment)

Total dose (Gy) Dose /fraction (Gy) BED2 (Gy)

63 1.8 60

59 1.7 54

56 1.6 49

52 1.5 42

Considerations

• Conc chemo: – Adds 12 Gy/ 2 Gy fractions (Kasibhatla et al,

IJROBP 2007)– Adds 7 Gy/2 (Fowler JF, IJROBP

• Very good prognosis patients, such as HPV-related oropharyngeal ca, may require quite low doses

How should we treat the low neck?

NTCP: Glottic edema grade 2+

Rancati T, IJROBP 2009

Extensive neck RT for non-laryngeal cancer, mostly no conc. chemo

No effort to spare the larynx/esophagus: High rates of dysphagia after whole-neck IMRT compared with split-field.

Fua et al, 2007

split field vs whole neck IMRT

Head Neck 2004

Amdur et al, Head Neck 2004

Laryngeal shield: do not extend caudally because jugular vein and nodes become more medial

Mendenhall, Amdur, Million, 1992

Extend the midline block to shield also inferior constrictor and esophagus

Caudell JJ IJROBP 2009

Whole neck IMRT or

upper neck IMRT + abutted AP low neck field

• Abutting AP low neck field: 30% of the recurrences were in the low neck – Chao et al IJROBP 2003

Whole-neck IMRT in cases of low neck involvement or high risk

Higher weight to targets or organs

• PTV doses: 99%-107% presc. doses• Larynx/constr./esophagus: reduce mean

dose as much as possible (<20 Gy)

– Targets weigh higer than organs

– Organs weigh higher than targets

PTVs (yellow/purple) weigh lower than larynx/inf. constrictor

PTVs (yellow) weigh higher than esophagus

The low neck

• Split-field technique is simpler, faster, less monitor units, likely less skin toxicity

• Whole-field IMRT allows better certainty in target coverage– may be preferable in cases of gross low neck

involvement or when the low neck is at high risk

Rosenthal et al, IJROBP 2008

Rosenthal et al, IJROBP 2008

Oral cavity

Not included in the cost function

Oral cavity

Included

Lt tonsillar cancer

After 23 fractions (GTV dose 46 Gy) concurrent with carboplatin+taxol

Estimated lip mucositis site dose 30 Gy/1.3 Gy/fraction

Mucosal point doses vs. length of time of mucositis

Narayan et al, IJROBP 2008;72:756

Lt tonsillar ca, chemo-RT: oral cavity outside the PTVs spared

Induction chemotherapy for HN cancer

Response to induction chemo:

CR 9%, PR 59%CR 17%, PR 55%

Patients proceed to chemo-RT after most tumors shrink by induction.

GTVs: the pre-chemo or the post-chemo volumes?

Neoadjuvant chemo: Its tumor effect may be trivial even if clinical CR is achieved.

Ian Tannock

After induction chemotherapy

• Use the pre-chemo targets• It is essential to examine the patient, have

adequate imaging studies, and preferably simulate the patient before chemo starts.

• Re-simulate after induction chemo and register the pre-chemo GTVs to the new planning CT.

• Same principle: do not reduce the GTV as tumor shrinks during RT.

Salama et al, IJROBP 2009

Acknowledgements• UM Rad-Onc residents, students & fellows

– Felix Feng– Mary Feng– Alex Lin– Siavash Jabbari– Laura Dawson– Aron Popovtzer– Iris Gluck

• Otolaryngol-HN Surgery– Doug Chepeha– Ted Teknos– Carol Bradford– Gregory Wolf

• Speech pathology– Teresa Lyden– Marc Haxer

• Dentistry– Carol-Anne Murdoch-Kinch– Jonathan Ship

• Rad-Onc Physics– Randall Ten Haken– Karen Vineberg– Dick Fraas

• NKI, Amsterdam– Marco Schwartz– Coen Rasch

Supported by NCI grants PO1 59827 and HN SPORE P50 CA/DE97248